Expression of retinoid-regulated genes in lamellar ichthyosis vs. healthy control epidermis: changes after oral treatment with liarozole
2009 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 89, no 1, 12-20 p.Article in journal (Refereed) Published
Lamellar ichthyosis is a keratinization disorder caused by TGM1, Ichthyin and several other gene mutations. A new treatment option is liarozole, which blocks the cytochrome P450 (CYP26)-mediated catabolism of endogenous all-trans retinoic acid. This study focuses on the expression of retinoid-related genes in ichthyotic epidermis before and after treatment with oral liarozole. We first compared the mRNA expression of cellular retinoic acid binding protein II (CRABPII), keratin (KRT) 2 and 4, CYP26A1 and B1, and two markers of inflammation (interleukin-1alpha and tumours necrosis factor (TNF)-alpha) in shave biopsies from 11 genetically defined, untreated patients and 12 age- and sex-matched healthy controls, finding no overt differences between the groups, besides elevated CRABPII expression. We then studied the biomarkers before and after 4 weeks of treatment with liarozole (75 or 150 mg/day), which produced a better therapeutic response in patients with Ichthyin (n=3) than in those with TGM1 (n=6) mutations. A significant decrease in the mRNA expression of KRT2 and TNF-alpha, and trends toward increased expression of KRT4 and CYP26A1 were observed in liarozole-treated patients, consistent with an increased retinoid stimulation of epidermis. However, there were no dose-related responses and the results of the immunostaining did not always parallel the mRNA findings. The results suggest that liarozole exerts a therapeutic effect in lamellar ichthyosis by mildly affecting the expression of retinoid- regulated genes in epidermis.
Place, publisher, year, edition, pages
2009. Vol. 89, no 1, 12-20 p.
retinoic-acid metabolism blocking agents, keratin, vitamin A metabolism, cytochrome P450, skin disorder
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-103992DOI: 10.2340/00015555-0573ISI: 000262563900004PubMedID: 19197536OAI: oai:DiVA.org:uu-103992DiVA: diva2:219170